This laboratory is interested in the relationship between protein sequence, structure and the mechanisms of protein folding and enzymic reactions. (i) Histidine Rich Proteins The malaria parasite, Plasmodium falciparum, produces large amounts of several histidine rich proteins of unknown structure. Their high concentrations of histidine distort their circular dichroic spectra, so that, unlike those of normal proteins, they cannot be interpreted in terms of secondary structures. We have reinvestigated the behaviour of poly L-histidine as a function of pH and solvent additives, and established a set of reference spectra under defined conditions, which can be used in analysis of the structures of these unusual proteins. (ii) Structure of Tryptophan Synthase (with S. Ashraf Ahmed and Edith Wilson Miles, LBP) We are investigating the conformational states of the tryptophan synthase alpha2-beta2 complex and of the separate alpha and beta subunits, using site directed mutagenesis. During catalysis, the enzyme changes from an open to a closed form, excluding solvent from the active site and facilitating chemical reactions. Analysis of a series of double mutants show that the more active closed form is stabilised by electrostatic interactions in the beta subunit. (iii) Structure of Mammalian Sulphotransferases. (with D. Marshall and W.B. Jakoby, LBM) The enzymatic activity of a phenol sulphotransferase, from rat liver, has been shown to be regulated by reversible oxidation/reduction of a conserved cysteine residue by physiological concentrations of glutathione. The two forms of the protein show differing complex patterns of inhibition by substrates and products, which indicate that the two active sites in the dimeric enzyme, although identical in sequence have very different chemical properties (half of sites reactivity).